Immune System + Cancer - TOKA Flashcards
What is cancer?
Imbalances in rate of cell division and cell death
Ex: Tumors happen when cells divide more rapidly than they die
What can cause transformation of cells, resulting in tumors?
- Carcinogens
- Radiation
- Viral infections
- Chronic inflamm.
- Genetic mutations
What are tumor-specific antigens?
Ag found on tumor cells but NOT on normal host cells
*** easier for IR to react and eliminate
What are tumor-associated antigens?
Ag expressed on tumor cells AND normal host cells
**makes it hard for Immune system to fight off
How do neutrophils respond to tumors?
by producing TNF-related apoptosis-inducing ligand
** stimulates apoptosis of tumor cells
How do NK cells help respond to tumors?
expresses NKG2D (activating receptor on NK cells) which binds to MICA and MICB stress molecules on tumor cells
*** leading to killing of tumor cell
Which macrophage type helps to kill tumor cells: M1 or M2?
Classically activated M1 helps kill many tumor cells
How do M2 macrophages play a role in tumors?
PROMOTES tumor growth (bad!!) by secreting
VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) + TGF-b
How do M1 macrophages kill tumor cells?
Through production of nitric oxide (NO)
How are macrophages activated to kill tumor cells?
Tumor-specific CD4+ T cells produce INF-y which activates M1 macrophages
How do CD8+ T cells help eliminate tumor cells?
Directly lyses tumor cells using perforins and granzymes
How do CD4+ T cells help eliminate tumor cells?
produces IFN-y to activate macrophages to kill tumor cells
How do NKT cells play a role in eliminating tumor cells?
NKT cells can recognize Ag presented on a non-classical MHC 1 molecule on tumor cells
How do antibodies help eliminate tumors?
Mediates killing by activating complement or by ADCC
(Ab binds to complement to start classical pathway)
How do tumor cells suppress/escape host immune responses?
Makes TGF-b which suppresses IR and induces PROLIFERATION + ANGIOGENESIS of tumor cells
** angiogenesis bc blood vessels feed the tumor + allow it to survive
-Tumor-activated DC secrete indoleamine (IDO) - suppresses T cells
- Secretes galectin-1 - stimulates angiogenesis
- Secretes PDL1 which suppresses T cell IR
Explain what tumor equilibrium is?
When the tumor cell is there but does not progress/proliferate
What are some approaches to tumor immunotherapy?
- Non specific Immune Stimulation
(Ex: BCG - releases pro inflamm cytokines to help IR) - Passive immunization
(Ex: monoclonal Ab against tumor Ag) - Active immunization
What is adoptive transfer?
When lymphocytes are removed from patient, inoculated with IL-2, then activated lymphocytes are injected back into the patient bearing the tumor
Tumor cells express PD-L1 which binds to PD-1 on CD8+ T cells to suppress their function. How can this be avoided?
Admin of Anti-PD-1 Ab
binds to PD-1 on CD8+ T cells to block tumor cell from binding PD-L1
